We estimate that in the United States, about 1 million people over the age of 55 are being medicated with nitrate ester (vasodilator drugs) and antihypertensive, antiarrhythmic, vasodilator and tranquilizing drugs. In this age group, these regimens are usually maintained for years. We have shown that, under conditions found in the stomach, drugs of the organic nitrate ester class, such as isosorbide dinitrate interact with therepautic doses of drugs such as propranolol (Inderal) and hydroxyzine (vistaril) to produce nitrosamines. Many nitrosamines are carcinogenic. This type of drug-drug interaction has not been described previously. We plan to study interactions between organic nitrate drugs and 14 drugs not previously investigated, such as propranolol, clonidine, guanethidine, N-acetylprocainamide, isoxuprine, dipyramidole and flurazepam. We plan to measure nitrosamines formed by these interactions in vitro and in animals. Mutagenicity and carcinogenicity of previously unidentified nitrosamines will be evaluated. This information will advance our knowledge of a new type of drug-drug interaction and illuminate its significance in elderly patients. It may be possible to prevent this type of drug-drug interaction by prescribing drugs at separate times or by using one drug instead of two. As a result of these studies, indiscriminate polypharmacy may be reduced; dosing schedules may change; and physicians will weigh the risks and benefits of extended drug therapy more carefully. The use of drugs in elderly patients may improve significantly.